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The human microbiota

The ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space”. Joshua Lederberg coined the term, emphasizing the importance of the microorganisms inhabiting the human body in health and disease.

Extensive research during recent years shows the importance of the microbiota to normal physiology: they are absolutely essential for effective digestion (releasing energy) and strong immune function (protecting us from serious disease). Scientists believe they play an important role in many other aspects of our health and well-being.

Why the microbiota is essential for our health

The microbiota is a very important component of our primary defense mechanism. Our skin and mucosa are colonized by trillions of microbes collectively known as the microbiota. Despite the enormous microbial population inhabiting the human body, including variable levels of potential harmful microbes (pathogens), most of us harbor these organisms without any signs of disease.

In order to survive in close proximity to these vast numbers of microbes, our epithelial tissues have several barrier functions that limit direct exposure to these microbes. For the skin, the major barrier is the epidermis which consists of several layers of cells that prevent pathogens reaching deeper skin tissues. In addition, the dry and slightly acidic environment on the external surface of the skin is inhospitable and prevents microbial growth. For mucosal surfaces, the mucus layer forms a protective barrier that prevents microorganisms from binding to the underlying cells.

When things go wrong in the microbiota we know about it.  Harmful microbes breach the protective layers and create imbalance (dysbiosis) by adhering or binding to human skin and mucosal tissues. This pathogenic adhesion is the first step on the path to infection.

A healthy microbiota is specifically important because the microbes:

  • prevent colonization by pathogens (competition)
  • attack pathogenic bacteria (biocides)
  • synthesize and excrete vitamins (nutrients for host cells)
  • stimulate the development of the immune system and the tissues and support the natural healing process

How harmful microbes bind to human tissues and cause imbalance (dysbiosis)

Good microbes (commensal and symbiotic microbes) live quietly in the outer skin and mucus layers and do not penetrate to deeper skin or mucus layers. These microbes do not have the tendency to bind to epithelial cells.  In contrast, most bad microbes (pathogens) have the ability to breach the mucus and skin barrier function and bind to and infect epithelial tissues. When pathogens succeed in getting through the skin or mucosal barriers, they use so-called ‘adhesion’ molecules to bind to receptors on the surface of our epithelial cells. Examples of sites where microbes can adhere to human cells are the urogenital tract, the digestive tract, the respiratory tract, skin and the eyes. Imbalanced conditions where harmful microbes dominate the microbiota and are able to cause problems at the epithelial surfaces of their host are called ‘dysbiosis’.

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When beneficial commensal microbiota are displaced by pathogens, a situation of dysbiosis occurs. The human body responds to this with an inflammatory reaction to attack the pathogens. This causes discomforts such as irritation, swelling or itch.

Situations of dysbiosis or imbalance often result in an inflammatory response which can cause symptoms such as itch, a burning sensation, redness and swelling. After initial adhesion, pathogenic microbes may proliferate and expand at the epithelial surface. While some pathogens can invade human tissues and cause serious infections after binding to epithelial cells, most situations of dysbiosis are self-limiting, meaning that it will not progress to serious infections, but they can be a cause of severe discomforts for the host.

An alternative to antibiotics

The use of antibiotics is indispensable to treat serious infections. However, also many less severe problems related to dysbiosis that don’t require (immediate) medication, are often treated with antibiotics.  Antibiotics can have serious drawbacks, including disturbance of the healthy microbiota and other potential negative side-effects. To reduce the need for antibiotics, it would be highly preferable to use non-antibiotic selfcare treatment for uncomplicated problems related to dysbiosis.

Anti-adhesion strategies to block infection

Anti-adhesive strategies are aimed at blocking the initial binding of microbes to human skin and mucosal tissues, to prevent infection in an early stage. Anti-adhesive therapies do not affect the viability of microbes and do not destroy the healthy microbiota (diagram).  Another advantage of this mode of action is the absence of selective pressure, which minimizes the risk of developing microbial resistance (diagram). Therefore, anti-adhesive agents can offer an interesting alternative approach  to antibiotic treatment of common health problems related to skin and mucosal microbial infections.

The human mucus layer uses anti-adhesion polysaccharides to prevent microbes binding to host tissues

The mucus layer that covers human epithelial surfaces is well-known for its natural anti-adhesion activity to prevent binding of microbes to the underlying epithelial cells (diagram). Our mucosal surfaces are a humid and warm environment that supports microbial growth. The digestive tract, the vagina and the mouth all contain extensive microbiota. To minimize direct contact with microbes, mucosal epithelial cells produce mucus that contains anti-adhesive polysaccharides. These polysaccharides trap microbes and prevent them from reaching the epithelial surface.

Natural polysaccharide anti-adhesion strategies

Polysaccharides from several natural sources are known for their anti-adhesion activity, with a mode of action similar to that described above for mucins. The protective effect of anti-adhesive polysaccharides has been demonstrated convincingly in a variety of in vitro studies and in vivo models with different pathogenic microbes. Therefore, anti-adhesive strategies offer a very promising, novel,  anti-microbial approach to be used as alternatives to antibiotics.

2QR-complex prevents adhesion of pathogens and restores the healthy microbiota

  • Microbes use adhesins to bind to polysaccharide structures on receptors of human cells.
  • Polysaccharides with structures similar to those of human cells can bind to microbes, and act as decoy to block interaction of harmful microbes with human cells.
  • In collaboration between BioClin and the Free University in Amsterdam, the 2QR-complex was identified as a natural and safe anti-adhesion polysaccharide fraction derived from gel of Aloe Barbadensis leaves.
  • The high diversity of polysaccharide structures in the patented 2QR-complex results in excellent anti-adhesion activity against many harmful microbial pathogens [18].
  • 2QR-complex blocks the adhesion of pathogenic microbes to human tissues but does not affect the growth of beneficial commensal microbes [19].Therefore, 2QR-complex treats and prevents binding of harmful microbes to human tissues and creates a situation with competitive advantage for commensals and corrects and restores the healthy microbiota.
  • 2QR-complex is harmless for human cells and tissues; it does not exert any chemical, metabolic or immunological response in the host tissues [20–22].

References

[18] Van Dijk, W., Goedbloed, A. F. & Koumans, F. J. R. NEGATIVELY CHARGED POLYSACCHARIDE DERIVABLE FROM ALOE VERA. Publication Date:29.09.2004Filing Date:23.12.2002. EP1461361. 1, 1–24 (2002).
[19] Kwakman, P. H. S. 2QR-complex polysaccharides do not affect microbial viability. Document on file. (2015).
[20] Celi, P. Method of fractionation of Aloe vera extract on basis of molecular weight and charge: Biological activity of the different fractions. Document on file.(2000).
[21] Van Dijk, W., Goedbloed, A. F. & Koumans, F. J. R. Negatively charged polysaccharide derivable form Aloe Vera. Freepatentsonline: EP20010205253Publication Date:07/02/2003 Filing Date:12/27/2001. (2001).
[22] Van Dijk, W. Further characterization of negatively charged polysaccharides isolated from concentrated Aloe vera gel with regard to antibacterial properties and molecular structure. Document on file. (2006).

2QR-complex in bio-active selfcare products for treatment of common microbial health problems

2QR-complex based products can be utilized as a first line treatment in correcting and restoring the microbiota and to treat the symptoms related to disturbed microbiota. They offer a novel and safe way to prevent microbial infections. 2QR-complex is not a medicine. Products based on the 2QR-complex are for treating common health problems and discomforts. For severe or advanced infections requiring immediate attention, medication is the best solution.

Each year many millions of 2QR-complex based products are sold in 60 countries around the world.  BioClin’s selfcare and over-the-counter products have been on the market since 1998 and many hold a leading market position.

Summary of the science

  • 2QR-complex polysaccharides derived from Aloe Barbadensis offer an innovative way to selectively neutralize pathogenic microbes by blocking their adhesion to the cells of skin and mucous tissue membranes.
  • By neutralizing pathogenic microbes, the beneficial commensal microbes can reestablish the healthy microbiota. As a result, 2QR-complex combats pathogenic microbes and corrects and restores the healthy microbiota.
  • This mode of action renders pathogenic microbes harmless in a natural and safe way, has no known side effects and does not provoke any microbial resistance.
  • In vitro and clinical studies show that 2QR-complex has potent anti-adhesion activity against different classes of pathogenic microbes.

2QR Research B.V. is an enterprise with main shareholders:

  • BioClin B.V.
  • The Free University, Amsterdam, The Netherlands
  • A combination of private investment funds

(background image by GrahamColm )